A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH)

This Phase 2/3 plus open-label extension study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of atumelnant treatment in pediatric participants with classic CAH. Part A is a Phase 2, open-label, semi-sequential cohorts portion of the study. Part B is the Phase 3, double-blind, randomized, placebo controlled confirmatory portion of the study. Part C is the open-label extension (OLE) portion of the study. Participants in Part A and B are eligible to enroll in Part C (OLE).

A total of approximately 153 participants may be enrolled in the study (planned and optional cohorts) ages 1 to < 18 years old.

The first 3 cohorts in Part A are for ages 12 to <18 years and will be semi-sequential, and Safety Review Committee (SRC) review of data and approval to proceed is required prior to enrolling each subsequent cohort. The fourth cohort in Part A is for ages 1 to 11 years old and will begin after Cohorts 1 and 2 have been completed, additional requirements are fulfilled, and following SRC review of Cohorts 1 and 2 data.

Inclusion criteria

Part A and B participants are eligible to be included in the study only if all of the following criteria apply:

• Male or female at birth, between 1 to <18 years of chronological age at the time of signing the Informed Consent Form (ICF).
• Have a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency (21-OHD) based on standard medically accepted criteria such as elevated 17-OHP level, confirmed CYP21A2 genetic testing, positive newborn screening with confirmatory second tier testing, or cosyntropin stimulation.
• Participants must have an elevated morning serum A4 level >ULN during Screening obtained prior to morning glucocorticoid (GC) administration.
• Participants must be on a stable supraphysiologic GC replacement therapy for at least one month prior to Screening.
• Compliance, as judged per Investigator discretion, with GC replacement and mineralocorticoid replacement (if applicable) regimen documented during the Screening Period.
• Biochemical euthyroidism as determined by the Investigator.

Part C inclusion criteria require participants to complete treatment in either Part A or Part B and in the Investigator's opinion it would benefit the participant to continue in Part C, regardless of age.

Exclusion criteria

Part A and Part B: Individuals in Part A and Part B who meet any of the following criteria will be excluded from participation in this study:

• Diagnosis of any form of CAH other than classic 21-OHD.
• Participants treated with other GCs within 30 days of Screening.
• Stress dose of GC therapy within 2 weeks of start of Screening, defined as any dose above the normal maintenance dose, including but not limited to intravenous (IV) or intramuscular (IM) hydrocortisone.
• Use of growth hormones within 1 week of start of Screening for short acting, or within 6 weeks of start of Screening for long acting.
• Use of a corticotropin-releasing factor receptor antagonist within 14 days of Screening.
• History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.
• Abnormal sleep/wake cycles (as determined by the Investigator).
• Female participants who are pregnant or lactating.
• Participants who have been dosed with an investigational drug (including atumelnant) in any prior clinical study within 60 days or 5 half-lives (whichever is longer) prior to the first dose.
• Individuals in Part C who do not meet the Part C Inclusion Criteria.